**5. Aptamer-based targeting**

Nanoconjugates functionalized with disease cell-specific aptamers have been reported to enhance specificity for microbial pathogens. Aptamers are single strands of intact sequences of nucleic or xeno nucleic acids. Because of their high affinity, selectivity, and specificity for specific microorganism targets, aptamers are selected and prepared, typically using the SELEX procedure [67] and used for NP functionalization [68]. The use of aptamers for the targeted delivery of anticancer drugs and PSs has been ubiquitously studied [69]. However, the use of aptamers for the targeted delivery of antibacterial drugs and PSs in aPDT has recently attracted attention [70]. Disease cell targeting aPDT applications may be illustrated with the studies of a DNAaptamer-functionalized nanographene oxide as a targeted nanomaterial-mediated bio-theragnostic approach against *Porphyromonas gingivalis*, a pathogenic periodontitis constituent of the periopathogenic complex [71]. Following synthesis and characterization, the nanographene oxide was functionalized with an aptamer [72], which was selected using the SELEX procedure [73, 74]. Using fluorescence flow cytometry, this study showed that graphene oxide NPs, functionalized with the DNA aptamer, enhanced target specificity of the nanoconjugate for *P. gingivalis* disease cells. In a similar study, aptamer-functionalized emodin NPs showed binding specificity and enhanced antibacterial activity against *Enterococcus faecalis* [75]. Regarding the applications of aptamers in aPDT, literature reviews have indicated that the effect of aptamers goes beyond disease cell targeting to include bactericidal and biofilm disruptive effects [76], suggesting that in addition to targeting specific bacterial pathogens, the aptamer-functionalized nanoconjugates could also exhibit bactericidal and biofilm disruptive effects.

### **6. Glycan-based targeting**

Evidence that the carbohydrate-based polysaccharide polymers found on bacterial cells, also known as glycans, can form the basis for bacterial targeting has been presented [77]. There are glycan-recognizing and binding proteins on bacterial target host cell surfaces, known as lectins. These protein molecules are recognized by the glycan structures on bacterial target host cell surfaces where the bacteria attach for host cell invasion [78]. The antibacterial macrophage strategy involves the initial attachment to the bacterial cell surface, followed by the delivery of depolymerases and lysins to degrade the bacterial cell wall-based glycans [79]. Similarly, the bacterial glycan cell targeting technology is based on extensively lectin-functionalized nanoconjugate systems that attract and selectively bind to bacteria with high binding affinity, delivering their antibacterial cargo, such as antibiotic chemotherapy drugs and PDT PSs, yet maintaining host microenvironment biocompatibility [80, 81].
